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Early Infantile Epileptic Encephalopathy-12 via the PLCB1 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
4215 PLCB1 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4215PLCB181479 81479(x2) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Eric Bend, PhD

Clinical Features and Genetics

Clinical Features

Early infantile epileptic encephalopathy-12 (EIEE12) is one of a group of severe, infantile onset seizure disorders. The clinical features of EIEE12 are heterogeneous. Three different reports assigned three different electroclinical diagnoses to patients with PLCB1 variants: early onset epileptic encephalopathy (EOEE), malignant migrating partial seizures of infancy (MMPSI), and non-specific EIEE (Kurian et al. 2010; Poduri et al. 2012; Ngoh et al. 2014). Shared features of these cases include onset of seizures between 10 weeks and 6 months of age with eye deviation, staring spells, lip smacking, drooling and tonic spasms of the upper limbs. Seizures could be brief, lasting several seconds, or prolonged, lasting minutes and requiring hospitalization. Patients experienced 10-20 seizures per day, and these seizures were highly resistant to treatment with anti-epileptic drugs. Abnormal EEG recordings seen in patients with EIEE12 included hypsarrhythmia and multifocal spikes (Kurian et al. 2010; Poduri et al. 2012; Ngoh et al. 2014). Developmental delay was noted prior to seizure onset and developmental regression was subsequently seen. All patients had severe cognitive and motor defects.

Genetics

EIEE12 is caused by variants in the PLCB1 gene and is inherited in an autosomal recessive manner. Large deletions and a splice site variant in PLCB1 have been documented to be pathogenic (Kurian et al. 2010; Poduri et al. 2012; Ngoh et al. 2014). PLCB1 encodes one of the four phospholipase C-beta enzymes in mammals. PLCB1 catalyzes the hydrolysis of the membrane component phosphatidylinositol-4-5-bisphosphate (PIP2) into the intracellular second messengers inositol-1,4,5-triphosphate (IP3) and diacylglycerol (DAG) (Bohm 2002). PLCB1 is highly expressed in the cerebral cortex and hippocampus and plays a key role in signal transduction across membranes. PLCB1 knockout mice exhibited delayed growth, failure to thrive, and died suddenly. Both recurrent seizure attacks with tonic extension of the body and status epilepticus were observed in PLCB1-/- mice; PLCB1 +/- mice were viable and fertile (Kim et al. 1997).

Clinical Sensitivity - Sequencing with CNV PG-Select

PLCB1 is a rare cause of EIEE. Two large scale studies which sequenced PLCB1 in patients with a variety of epilepsy syndromes did not identify any PLCB1 variants in ~550 patients (Kodera et al. 2013; Carvill et al. 2013). In addition, follow up sequencing in 27 families with phenotypes resembling EIEE12 did not identify any PLCB1 variants (Kurian et al. 2010; Poduri et al. 2012).

Testing Strategy

This test provides full coverage of all coding exons of the PLCB1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

PLCB1 testing should be considered in patients with drug-resistant EIEE of unknown cause, particularly if autosomal recessive inheritance is suspected. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PLCB1.

Gene

Official Gene Symbol OMIM ID
PLCB1 607120
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Epileptic Encephalopathy, Early Infantile, 12 AR 613722

Citations

  • Bohm D. 2002. Disruption of PLC-beta 1-Mediated Signal Transduction in Mutant Mice Causes Age-Dependent Hippocampal Mossy Fiber Sprouting and Neurodegeneration. Molecular and Cellular Neuroscience 21: 584–601. PubMed ID: 12504592
  • Carvill GL, Heavin SB, Yendle SC, McMahon JM, O’Roak BJ, Cook J, Khan A, Dorschner MO, Weaver M, Calvert S, Malone S, Wallace G, Stanley T, Bye AM, Bleasel A, Howell KB, Kivity S, Mackay MT, Rodriguez-Casero V, Webster R, Korczyn A, Afawi Z, Zelnick N, Lerman-Sagie T, Lev D, Møller RS, Gill D, Andrade DM, Freeman JL, Sadleir LG, Shendure J, Berkovic SF, Scheffer IE, Mefford HC. 2013. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. Nature Genetics 45: 825–830. PubMed ID: 23708187
  • Kim D, Jun KS, Lee SB, Kang NG, Min DS, Kim YH, Ryu SH, Suh PG, Shin HS. 1997. Phospholipase C isozymes selectively couple to specific neurotransmitter receptors. Nature 389: 290–293. PubMed ID: 9305844
  • Kodera H, Kato M, Nord AS, Walsh T, Lee M, Yamanaka G, Tohyama J, Nakamura K, Nakagawa E, Ikeda T, Ben-Zeev B, Lev D, Lerman-Sagie T, Straussberg R, Tanabe S, Ueda K, Amamoto M, Ohta S, Nonoda Y, Nishiyama K, Tsurusaki Y, Nakashima M, Miyake N, Hayasaka K, King MC, Matsumoto N, Saitsu H. 2013. Targeted capture and sequencing for detection of mutations causing early onset epileptic encephalopathy. Epilepsia 54: 1262–1269. PubMed ID: 23662938
  • Kurian MA, Meyer E, Vassallo G, Morgan NV, Prakash N, Pasha S, Hai NA, Shuib S, Rahman F, Wassmer E, Cross JH, O’Callaghan FJ, et al. 2010. Phospholipase C beta 1 deficiency is associated with early-onset epileptic encephalopathy. Brain 133: 2964–2970. PubMed ID: 20833646
  • Ngoh A, Mctague A, Wentzensen IM, Meyer E, Applegate C, Kossoff EH, Batista DA, Wang T, Kurian MA. 2014. Severe infantile epileptic encephalopathy due to mutations in PLCB1: expansion of the genotypic and phenotypic disease spectrum. Developmental Medicine & Child Neurology n/a–n/a. PubMed ID: 24684524
  • Poduri A, Chopra SS, Neilan EG, Christina Elhosary P, Kurian MA, Meyer E, Barry BJ, Khwaja OS, Salih MAM, Stödberg T, Scheffer IE, Maher ER, et al. 2012. Homozygous PLCB1 deletion associated with malignant migrating partial seizures in infancy: PLCB1 Deletion Causes MMPEI. Epilepsia 53: e146–e150. PubMed ID: 22690784

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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